Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non–MSI-H/non–dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results

David M. O'Malley, Giovani M. Bariani, Philippe A. Cassier, Aurelien Marabelle, Aaron R. Hansen, Ana De Jesus Acosta, Wilson H. Miller, Tamar Safra, Antoine Italiano, Linda Mileshkin, Lili Yao, Alexander Gozman, Fan Jin, Michele Maio

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

Résumé

Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non–MSI-H/non–dMMR advanced EC (cohort D). Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of January 12, 2022, median (range) follow-up in the MSI-H/dMMR (n = 94) and non–MSI-H/non–dMMR (n = 96) groups was 54.5 (14.7–71.4) and 68.3 (64.3–71.9) months, respectively. The ORR (95 % CI) was 50 % (40 %–61 %) in the MSI-H/dMMR group; 15 patients (16 %) experienced a complete response, 32 (34 %) experienced a partial response. The ORR (95 % CI) in the non–MSI-H/non–dMMR group was 7 % (3 %–14 %); 7 patients (7 %) experienced a partial response, none experienced a complete response. The estimated 4-year DOR rates were 66 % and 56 %, respectively. Median PFS was 13.1 (95 % CI, 4.3–25.7) months in the MSI-H/dMMR group and 2.1 (95 % CI, 2.1–2.2) months in the non–MSI-H/non–dMMR group. Median OS was 65.4 (95 % CI, 29.5–not reached) and 11.1 (95 % CI, 8.1–15.3) months, respectively. Toxicity was manageable in both groups. Conclusions: These results continue to support pembrolizumab as a standard-of-care option for MSI-H/dMMR advanced EC in patients with disease progression following prior systemic therapy who are not candidates for curative surgery or radiation.

langue originaleAnglais
Pages (de - à)130-135
Nombre de pages6
journalGynecologic Oncology
Volume193
Les DOIs
étatPublié - 1 févr. 2025

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